Análise da via Wnt e seu envolvimento no processo da tumorigênese do câncer colo-retal

• Autor(a) principal: Vidal, Flávia Castello Branco
• Data de Publicação: 2010
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/7772
• topic: Colorectal cancer; Wnt/β-catenin pathway; EGFR; GSK3-β; β-catenina; Claudin-1; Tumoral progression; Câncer colo-retal; Via Wnt; EGFR; GSK3-β; β-catenina; Claudina-1; Progressão tumoral; Cancer; Adenocarcinoma; CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA

Colorectal cancer (CCR) represents the fourth type of cancer most common in Brazil among men and women and the survival for this tumor type is considered good if the disease is diagnosed at early stage. The progression of an adenoma (benign tumor) to an adenocarcinoma (malign tumor) is dependent on the accumulation of mutations in a variety of oncogenes and tumors suppressors genes. These mutations can lead to alterations of important cell signaling pathways that control these events, such as Wnt e EGFR. However, the molecular and cellular mechanisms mediated by these pathways during CCR progression remain to be defined. In the present study we assesses the role that Wnt and EGFR pathway play during CCR progression using Caco-2 cells, a human cell line derived of colorectal cancer, as a model. Cells were treated with EGF, an EGFR pathway activator, and lithium chloride, (LiCl) a known inhibitor of the enzyme GSK-3β and, therefore a Wnt pathway activator or alternatively by using combination of both drugs. After treatments, we monitored cell morphology, localization and expression of junctional proteins, proliferative and cell cycle patterns, and the tumorigenic potential (cell migration and colony formation). We show that subcellular localization of the junctional proteins claudin-1 and β-catenin was altered after treatment with EGF and LiCl, however the expression were not affected. Nuclear localization of β-catenin, a marker of Wnt pathway activation, was observed after treatment with both compounds, however these agents modulated in a differential fashion the enzyme GSK-3β. Furthermore, EGF treatment increased the proliferative and migratory capacity of the cells, but did not alter colony formation potential. LiCl, despite being a known activator of the Wnt pathway, inhibited the increase of proliferation and migration caused by EGF, as demonstrated by the cell treatments with EGF+LiCl, and reduced the cell colony formation. Our results reveal that LiCl present a suppressor tumor activity, which may represent a new role for this compound as potential therapeutic agent in the CCR treatment.